Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
Brain Korea 21 Plus Project for Biomedical Science, Korea University College of Medicine, Seoul, Republic of Korea.
Oncoimmunology. 2023 Mar 17;12(1):2190671. doi: 10.1080/2162402X.2023.2190671. eCollection 2023.
Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Here, we show that targeting an ETS transcription factor ELK3 (ELK3) recruits immune cells including natural killer (NK) cells into tumors via the chemotactic activity of chemokine. ELK3 depletion increases CXCL16 expression level and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment in TNBC. analysis showed that is negatively correlated with expression in breast cancer patient samples. Low expression of and high expression of were associated with a better prognosis. Low expression of and high expression of were associated with increased expression of NK cell-related genes. Our findings demonstrate that the ELK3-CXCL16 axis modulates NK cell recruitment to increase NK cell cytotoxicity, suggesting that targeting the gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC.
三阴性乳腺癌（TNBC）是最具挑战性的乳腺癌亚型，因为其侵袭性行为和可用的治疗策略有限。在过去的十年中，免疫疗法已成为延长晚期实体瘤包括 TNBC 患者生存的一种有前途的治疗方法。然而，免疫疗法在实体瘤中的疗效仍然有限，因为实体瘤中浸润的淋巴细胞很少。在这里，我们表明靶向 ETS 转录因子 ELK3（ELK3）通过趋化因子的趋化活性将免疫细胞包括自然杀伤（NK）细胞招募到肿瘤中。ELK3 耗竭通过 CXCL16 介导的 NK 细胞募集增加了 TNBC 中 CXCL16 的表达水平并促进了 NK 细胞的细胞毒性。 分析表明， 在乳腺癌患者样本中与 的表达呈负相关。 的低表达和 的高表达与更好的预后相关。 的低表达和 的高表达与 NK 细胞相关基因的表达增加相关。我们的研究结果表明，ELK3-CXCL16 轴调节 NK 细胞的募集以增加 NK 细胞的细胞毒性，这表明靶向 基因可能是增加 TNBC 中免疫疗法疗效的辅助策略。
